LSN3074753
LSN3074753, an analog of LY3009120 (HY-12558), is a pan-RAF and Raf dimer inhibitor. LSN3074753 demonstrates activity against tumor cells with MAPK pathway activation driven by BRAF monomer or RAF dimers including BRAF- or KRAS-mutant colorectal cancer. LSN3074753 combined with Cetuximab (HY-P9905) shows additive and synergistic effects for colorectal cancer PDX models, particularly those with KRAS or BRAF mutation.
For research use only. We do not sell to patients.
- CAS No.: 1455031-68-1
- Formula: C24H30FN5O2
- Molecular Weight:439.53
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
Cellular Effect
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Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| A-375 | ED50 |
1.7 mg/kg
Compound: 6
|
In vivo inhibition of BRAF V600E mutant in human A375 cells xenografted in po dosed athymic nu/nu mouse assessed as inhibition of ERK phosphorylation by ELISA
In vivo inhibition of BRAF V600E mutant in human A375 cells xenografted in po dosed athymic nu/nu mouse assessed as inhibition of ERK phosphorylation by ELISA
|
[PMID: 25965804] |
| A-375 | IC50 |
0.01 μM
Compound: 6
|
Antiproliferative activity against human A375 cells after 72 hrs by resazurin assay
Antiproliferative activity against human A375 cells after 72 hrs by resazurin assay
|
[PMID: 25965804] |
| A-375 | IC50 |
0.022 μM
Compound: 6
|
Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ERK phosphorylation measured after 72 hrs by ELISA assay
Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ERK phosphorylation measured after 72 hrs by ELISA assay
|
[PMID: 25965804] |
| HCT-116 | IC50 |
0.16 μM
Compound: 6
|
Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA
Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA
|
[PMID: 25965804] |
| HCT-116 | IC50 |
0.174 μM
Compound: 6
|
Antiproliferative activity against human HCT116 cells after 67 hrs by resazurin assay
Antiproliferative activity against human HCT116 cells after 67 hrs by resazurin assay
|
[PMID: 25965804] |
Chemical Information
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CAS No. 1455031-68-1
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Molecular Weight 439.53
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Formula C24H30FN5O2
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SMILES
O=C(NC[C@@H](O)C(C)(C)C)NC1=CC(C2=CC3=CN=C(NC)C=C3N=C2C)=C(C)C=C1F
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Genotoxicity/Mutagenicity Study
The bacterial reverse mutation assay detects point mutations that restore amino-acid prototrophy in auxotrophic Salmonella typhimurium or Escherichia coli tester strains; after exposure to a test article, mutagenic activity is read out as an increased number of revertant colonies on minimal agar compared with the vehicle control. The assay uses tester strains with different mutation targets so that base-substitution and frameshift mutagens can be detected, and testing is performed with and without exogenous mammalian metabolic activation because some chemicals require biotransformation to become mutagenic.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)